1. Field of the Invention
The present invention relates to the use of analogs of thrombomodulin ("TM") that have the ability to enhance the thrombin-mediated activation of protein C but which have a significantly reduced ability to inhibit the direct procoagulant activities of thrombin, such as, for example, thrombin-mediated conversion of fibrinogen to fibrin. These analogs are useful in, for example, antithrombotic therapy. Novel proteins, nucleic acid gene sequences, pharmaceuticals and methods of inhibiting thrombotic activity are disclosed. Included are methods for increasing the circulating half life of the proteins.
There are many disease states that would benefit from treatment with a safe and effective anticoagulant/antithrombotic. The nature of these conditions varies. For example, anticoagulant therapy is useful in acute conditions such as during thrombolytic therapy in myocardial infarction or in treatment of disseminated intravascular coagulation (DIC) associated with, for example, septicemia. Anticoagulants are also useful for less acute conditions, such as chronic use in patients that have received heart valve implants or prophylactic use in surgery patients to reduce the risk of deep venous thrombosis (DVT).